We propose conducting a population-based study to explain the regional variation in breast cancer rates in Wisconsin that will build upon past and ongoing case-control studies of breast cancer at the University of Wisconsin Comprehensive Cancer Center. We hypothesize that the regional variations in breast cancer rates in Wisconsin are due to regional variations in established or potential breast cancer risk factors. The specific aims include 1) comparing breast cancer incidence, mortality, and survival rates within Wisconsin by geographic area; 2) evaluating the contribution of previously identified breast cancer risk factors, socioeconomic status, and screening practices to the regional variations in breast cancer rates; and 3) evaluating the association between environmental exposures (such as PCBs, DDT, and other xenoestrogens) and breast cancer risk, and if associated, the contribution of these exposures to the regional variations in breast cancer rates. In Phase I, we assign a "geographic breast cancer risk" to every case and control already enrolled in our case-control studies (n=14,000) by analyzing breast cancer mortality and incidence rates by area of residence (county, city, zip code, and census tract). Next, we will adjust this risk by controlling for established and potential individual-and community-level risk factors for breast cancer. In Phase II, we will expand our ongoing case-control study (n=6,600) by collecting information on environmental exposures and determining their contribution to the regional variation in breast cancer rates. Biologic specimen collection currently (buccal smears) and proposed (blood) will enable us to evaluate genetic risk and markers of biologic exposure. By utilizing existing populations, protocols, personnel, and software, we can complete these evaluations in an efficient, timely, and statistically valid manner. This approach will enable us, in collaboration with the NCI, NIEHS, and other funded researchers, to examine in detail the contribution of a variety of individual- and community-level exposures to the long-standing regional variation in breast cancer rates in Wisconsin and will improve our understanding of the causes of breast cancer.